4-Fluoro-3-methylbenzaldehyde → 8-(4-Fluoro-3-methylphenyl)oct-7-enoic acid

To a suspension of 7-Carboxyheptanyltriphenylphosphonium bromide (9.240 g, 19.602 mmol) in 100 mL of benzene, was added t-BuOK (58.8 mL, 58.8 mmol, 1M in THF). The resulting mixture was refluxed for 1 h and then 4-fluoro-3-methylbenzaldehyde (1.43 mL, 11.761 mmol) was added via a syringe. The mixture was continued to reflux under N2 for 63 h. After cooling to room temperature, the reaction mixture was washed with water (80 mL). The aqueous layer was acidified with concentrated HCl to pH=2 and extracted with ethyl acetate (30 mL×3). The combined organic extracts were dried (Na2SO4), filtered, and concentrated under reduced pressure. The product was isolated by Flash column chromatography (silica gel column) eluting with 0-30% ethyl acetate/hexanes to give the title compound as colorless oil (3.150 g, >99% yield). LC-MS: tR=9.6 min, m/z 251 (M+H)+.

1. temperatureThe resulting mixture was refluxed for 1 h
2. temperatureto reflux under N2 for 63 h
3. washthe reaction mixture was washed with water (80 mL)
4. extractionextracted with ethyl acetate (30 mL×3)
5. dry with materialThe combined organic extracts were dried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe product was isolated by Flash column chromatography (silica gel column)
9. washeluting with 0-30% ethyl acetate/hexanes

ORD record

ord-f58fe6287b2e4c8cb16d15630dd6e060

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07807720B2